How the brain works
Introductions to six core topics in brain science: connectivity, nerve signals, synapses, neuroplasticity, brain rhythms and glial cells. Each topic covers the main concepts and the changes that occur in disease. Technical terms are defined in the glossary.
Connectivity
The human brain contains roughly 86 billion neurons. Its function depends as much on how they are connected as on their number.
Each neuron sends a single output fibre, the axon, and receives input through many branching dendrites. Axons can be short, linking neighbouring cells, or very long, connecting distant regions. Bundled together, long axons form the brain’s white matter. Its tracts link the two hemispheres, connect the cortex with deeper structures and carry signals to and from the spinal cord; the largest, the corpus callosum, links the left and right hemispheres.
This wiring allows regions with different specialisations to work together. The recognition of a familiar face, for example, engages visual areas at the back of the brain, memory systems in the temporal lobe and emotional circuits deep within it, all within a fraction of a second.
Researchers describe this organisation as a network, and the complete map of the brain’s connections as its connectome. Some regions act as hubs: they are connected to many others and help to integrate information across the brain. Mapping the connectome is one of the central goals of modern neuroscience.
In disease
Damage to white-matter pathways, through stroke, traumatic brain injury or multiple sclerosis, can disrupt communication between regions even when the regions themselves are intact. Changes in large-scale connectivity are also being studied in conditions such as Alzheimer’s disease, schizophrenia and depression.
Nerve signals
Neurons communicate with brief electrical impulses called action potentials. Many nerve fibres are insulated so that these impulses travel quickly.
An action potential is a rapid, all-or-none change in voltage across the neuron’s membrane, produced as ion channels open and close in sequence: sodium ions enter the cell, then potassium ions leave it. The impulse then regenerates along the axon, point by point.
Many axons are wrapped in myelin, a fatty insulating sheath formed by glial cells: oligodendrocytes in the brain and spinal cord, and Schwann cells in the peripheral nerves. The sheath is interrupted at regular gaps called nodes of Ranvier. The impulse effectively jumps from node to node, a process called saltatory conduction, which is far faster and more energy-efficient than conduction along an unmyelinated fibre.
Thick, heavily myelinated fibres conduct fastest, reaching speeds of tens of metres per second or more, while thin unmyelinated fibres conduct at around a metre per second. These differences explain why a sharp pain is felt before a dull, aching one.
In disease
In multiple sclerosis, the immune system attacks myelin in the brain and spinal cord, slowing or blocking signals and causing symptoms such as weakness, numbness and visual problems. In Guillain–Barré syndrome, peripheral nerve myelin is affected.
Synapses and memory
Neurons communicate at junctions called synapses. At a chemical synapse the two cells do not touch: an electrical signal is converted into a chemical one, which crosses a narrow gap and is converted back into an electrical signal.
When an action potential reaches the end of an axon, it triggers the release of neurotransmitter molecules from small vesicles into the synaptic cleft. The transmitter crosses the gap in a fraction of a millisecond and binds receptors on the receiving neuron, opening ion channels or starting chemical signalling inside the cell. Most synapses in the brain are chemical; a minority are electrical.
Some transmitters excite the receiving neuron, making it more likely to fire; others inhibit it. Glutamate is the main excitatory transmitter in the brain and GABA the main inhibitory one, and the balance between excitation and inhibition keeps brain activity stable. Other transmitters, such as dopamine and serotonin, adjust the activity of whole circuits and influence mood, motivation and attention.
A single neuron can receive thousands of synaptic inputs, and the strength of each connection can change with experience. These changes are thought to be the cellular basis of learning and memory.
In disease
Disrupted synaptic function is implicated in many conditions. Synapse loss is an early feature of Alzheimer’s disease, an imbalance between excitation and inhibition contributes to epilepsy, and altered transmitter signalling is involved in depression, addiction and Parkinson’s disease. Many medicines act at synapses, for example by changing how transmitters are released, broken down or taken back up.
Neuroplasticity
Neuroplasticity is the capacity of the brain to change its connections throughout life in response to learning, experience and injury.
When two connected neurons are repeatedly active together, the synapse between them can become stronger, an effect known as long-term potentiation. Connections that are rarely used can weaken. These changes in synaptic strength are a central mechanism of learning and memory.
Plasticity is also structural. Neurons can grow new dendritic spines and branches, form new synapses and remove others. Early in life the brain is especially plastic, and some abilities, such as normal binocular vision, depend on experience during sensitive periods in childhood.
Plasticity continues in adulthood, although it changes with age. Whether new neurons are formed in the adult human hippocampus, and to what extent, remains an active area of research.
In disease
After a stroke, surviving regions can take over some functions of damaged areas, which is why intensive rehabilitation helps recovery. Plasticity can also be maladaptive, contributing for example to chronic pain or to the persistence of addiction.
Brain rhythms
Large groups of neurons often fire together in rhythmic patterns, producing waves of electrical activity that can be recorded from the scalp.
These oscillations are described by their frequency. Slow delta waves dominate deep sleep; theta rhythms are prominent during drowsiness and in memory-related activity of the hippocampus; alpha rhythms appear during relaxed wakefulness with the eyes closed; faster beta and gamma rhythms accompany active thinking and focused processing.
Rhythms are thought to help coordinate communication between brain regions, timing when groups of neurons are most receptive to input. They change systematically across the stages of sleep, which is how sleep is scored in a sleep laboratory.
Electroencephalography (EEG) records these rhythms with millisecond precision. It is inexpensive, safe and portable, which makes it one of the most widely used tools in clinics and research.
In disease
In epilepsy, populations of neurons fire in abnormally synchronised bursts, which appear on the EEG as spikes and sharp waves. EEG is also used to assess sleep disorders, monitor brain function during anaesthesia and intensive care, and study changes in conditions such as dementia.
Glial cells
The brain contains roughly as many glial and other non-neuronal cells as neurons. They are essential to brain function.
Astrocytes, star-shaped cells, supply neurons with energy, regulate the chemical environment around synapses, recycle neurotransmitters and help maintain the blood–brain barrier. A single astrocyte can contact a very large number of synapses.
Oligodendrocytes produce the myelin that insulates axons in the brain and spinal cord, allowing fast signalling, and also support axons metabolically. Microglia are the brain’s resident immune cells: they survey the tissue, remove debris and dying cells, and prune unneeded synapses during development.
Other glial cells line the fluid-filled ventricles, and in the peripheral nervous system Schwann cells form myelin around nerve fibres.
In disease
Glial cells are increasingly recognised as contributors to disease. Microglial responses are strongly implicated in Alzheimer’s disease, the loss of oligodendrocytes and myelin underlies multiple sclerosis, and the most common malignant brain tumours, gliomas, arise from glial lineages.
Questions and answers
Answers to common questions about the brain and its disorders.
How do neurons communicate with one another?
Neurons transmit information electrically along their membranes and chemically between cells. An action potential, a brief, all-or-none reversal of membrane voltage generated by voltage-gated sodium and potassium channels, propagates along the axon. At the axon terminal, it triggers calcium-dependent release of neurotransmitter into the synaptic cleft, where the transmitter binds receptors on the postsynaptic neuron and alters its excitability.
What roles do glial cells play in the nervous system?
Glial cells are approximately as numerous as neurons in the human brain and are essential to its function. Astrocytes regulate the extracellular environment, clear neurotransmitters and contribute to the blood–brain barrier; oligodendrocytes form the myelin sheath around axons in the central nervous system; and microglia act as resident immune cells that respond to injury and help refine synaptic connections during development.
How are memories formed and consolidated?
Long-lasting changes in synaptic strength, of which long-term potentiation is the best-characterised example, are considered the principal cellular basis of learning and memory. The hippocampus is critical for encoding new declarative memories. Over time, a process termed systems consolidation gradually reorganises these memories into distributed networks in the neocortex, and sleep is thought to make an important contribution to this process.
Does the adult brain retain the capacity for plasticity?
Yes. Neuroplasticity, the capacity of the nervous system to reorganise its structure and function in response to experience, persists throughout life, although certain forms are most pronounced during developmental critical periods. Adult plasticity underpins learning and much of the recovery observed after stroke or brain injury. The extent of adult neurogenesis in the human brain, by contrast, remains a matter of active scientific debate.
What occurs in the brain during an epileptic seizure?
A seizure is a transient episode of abnormal, excessive or synchronous neuronal activity. Focal seizures originate within networks limited to one hemisphere, whereas generalised seizures engage networks in both hemispheres from the outset. Epilepsy is diagnosed when a person has an enduring predisposition to seizures, typically demonstrated by two unprovoked seizures occurring more than 24 hours apart.
Why is migraine classified as a neurological disorder?
Migraine is a primary headache disorder with a distinct neurobiological basis, rather than a severe form of ordinary headache. Attacks involve activation of the trigeminovascular system and the release of neuropeptides such as calcitonin gene-related peptide (CGRP), which is now the target of several preventive treatments. The visual aura experienced by some patients is associated with cortical spreading depolarisation, a slowly propagating wave of neuronal and glial depolarisation.
What pathological changes characterise Alzheimer’s disease?
The defining features are extracellular plaques composed of amyloid-β and intracellular neurofibrillary tangles of hyperphosphorylated tau, accompanied by synaptic loss, neuroinflammation and progressive neuronal death. These changes typically emerge first in the entorhinal cortex and hippocampus, which accounts for the early impairment of recent memory, and they begin many years before clinical symptoms become apparent.
Why is sleep important for brain function?
Sleep is an active, highly regulated state that supports the consolidation of memory and the regulation of synaptic strength. Studies, predominantly in animal models, also indicate that sleep enhances the clearance of metabolic waste products from the brain. Chronic sleep disruption is associated with impaired cognition, altered mood and an increased risk of several neurological and psychiatric disorders.
What is the blood–brain barrier, and why does it matter for treatment?
The blood–brain barrier is a highly selective interface formed by specialised endothelial cells joined by tight junctions, supported by pericytes and astrocytic end-feet. It protects neural tissue from toxins and pathogens and maintains a stable chemical environment. The same selectivity, however, prevents many therapeutic compounds from reaching the brain, making drug delivery a central challenge in treating neurological disease.
Research design
How studies are designed, and how a relationship between two variables is distinguished from a causal effect.
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